Innovating Your Drug Discovery

Phenotypic Profiling is on the Rise!

Three terrific review articles that explain why pharma is moving from target to phenotype

For some years now, there has been a paradigm shift to augment the one-dimensional focus of target-based assays with approaches that take a more holistic look at the effects of drug candidates. Phenotypic profiling is seeing a resurgence, and with it a lot of really great literature on the subject. The below are just three of our favorite reviews that explain why many drug developers are turning to phenotype for answers.

Developing predictive assays: The phenotypic screening “rule of 3”

An outstanding article that outlines what makes for a good, predictive, phenotypic assay was written by Fabian Vincent, et al. and published in Science Translational Medicine. The authors break down a good assay into three criteria:

  1. “Disease relevance of the assay system”
  2. “Disease relevance of the stimulus”
  3. “Assay readout proximity to the clinical end point”

A very well-written review with great examples from the literature.

Vincent, F, et al. Developing predictive assays: The phenotypic screening “rule of 3”. Science Translational Medicine 24 Jun 2015: Vol. 7, Issue 293, pp. 293ps15

Phenotypic screening, take two

A few years old now, but still relevant. Joanne Kotz from the Nature Publishing Group explains why some big companies like GlaxoSmithKline and Novartis made the turn toward phenotypic screening and highlights some of the challenges associated with a reliance on target-based data.

Kotz, J. Phenotypic screening, take two. SciBX 5(15)

The Power of Sophisticated Phenotypic Screening and Modern Mechanism-of-Action Methods

It should come as no surprise that Mechanism of Action (MOA) is the elusive final question for a lot of drug developers. Here Wagner and Schreiber outline a number of current methods to deconvolute MOA. Most interesting (to us at DiscoverX at least) is the use of computational methods to classify molecules based on their phenotypic similarity to other, known, small molecules (or biologics).

Wagner and Schreiber, The Power of Sophisticated Phenotypic Screening and Modern Mechanism-of-Action Methods, Cell Chemical Biology (2016)